Alzheimer's disease (AD) is a degenerative brain disease which occurs in 11% of the older population aged 60 and older, and the number of patients increases rapidly as the population ages. AD has a significant impact on quality of life and economic losses of medical expenses, etc. (WHO Report, 2010). The treatment methods and drugs for AD relate to slowing down the progression of the disease and alleviate its symptoms, rather than fundamentally preventing the disease. There, it is very necessary and significant to alleviate patients' pain and reduce social costs incurred in relation with the disease, by providing appropriate treatment to the patients through early diagnosis. As current diagnostic methods, gene tests, cerebrospinal collection, PET or MRI, etc., are used. However, these methods are not only expensive but also invasive, which is burden to patients. Also, the representative AD biomarker known up to now is beta amyloid, which is aggregated in the brain and is a direct cause of onset AD. Meanwhile, recently, the research on other biomarkers is actively proceeding using advanced analysis apparatus.
Meanwhile, there are many concerns in biosensors which can quickly and simultaneously detect artificial aptamers, modified proteins, toxins, etc., in addition to naturally occurring molecules including naturally occurring DNA, RNA, protein, virus, or pathogen. The development of biosensor technologies helps promoting various medical fields, such as discovery of drugs, detection of genetic mutants, and evaluation on treatment effect of genes.
Biosensors using field effect transistors (FETs), which were first invented in the 1970s, sense a change in environment through a change in current between two places with respect to one reference place, using a source electrode, a drain electrode, and a gate electrode of the FET. Upon reviewing its principles, electrochemical potential difference in the interface between a solution and a sensing membrane varies depending on ion concentration in the solution. The change in potential difference generates a change in voltage in an effective gate region caused by a change in threshold voltage, and this change modifies channel conductivity, which causes a change in current of the drain electrode. The change in concentration of a particular ion present in the solution can be detected by measuring the change in current of the drain electrode, and the formation of an ion sensing membrane selectively sensitive to the particular ion can lead to the preparation of a sensor capable of sensing various ions. Biosensors using the FET can mount numerous sensing elements on one chip, thereby allowing multidimensionalization by arranging same type of multiple sensors and multifunctionalization by arranging different types of multiple sensors. Also, the biosensors can be intellectualized by mounting intellectual circuits, or mounting relevant circuits and devices, to be systematized. There, they draw attention as high-tech sensors.
Drosophila has well developed olfactory and gustatory sensory receptors, its genetic information is well known, and chemo sensory receptors present in cell surface sensitively react with particular smell or taste. There, when drosophila cells are used as a sensing substance, the sensitivity and selectivity may be optimized.
Accordingly, the present inventors analyzed the saliva of patients using GC-MS for searching for noninvasive AD biomarkers and found sugar components which are substances variously and specifically appearing in patients with brain disorders, to select the substances as a new biomarker for AD, and prepared a drosophila cell based ion-sensitive field effect transistor (ISFET) biosensor. Further, the present inventors confirmed that the biosensor sensitively reacts with trehalose, which is one of the sugar components, and in the saliva of the patients with AD, thereby completing the present invention.